DESCRIPTION: (Applicant's Abstract) The treatment of HIV-infected people within prison poses a significant challenge. A minimum of 5 percent of the HIV infected people in the United States are incarcerated (1,2) and a significant proportion of these have a history of drug, and/or alcohol dependence (13). Preliminary observations suggest that HIV-infected prison inmates have much higher AIDS-related mortality than matched populations outside of prison (3). Although highly active antiretroviral therapy (HAART) holds great promise in improving important clinical outcomes, difficulties with adherence appear to play a significant role in treatment failure. Directly observed therapy (DOT) is a potential mechanism to promote adherence. In the North Carolina Department of Corrections, all inmates on HAART receive HIV protease inhibitors by DOT. Although DOT is an attractive strategy, neither the level of adherence to HAART in prison nor the efficacy of DOT has been extensively evaluated. Our preliminary studies demonstrate that DOT has significant untoward effects for inmates and may be of limited utility in promoting adherence in a prison setting. The potential for a dramatic virologic response as well as the consequences of inadequate adherence for both the individual inmate and for transmission of resistant viruses makes an understanding of the adherence in this setting especially urgent. In a collaborative effort between investigators at the Centers for AIDS Research of UNC and UCLA, we will perform a comprehensive assessment of DOT among inmates with a history of substance abuse. We will determine the impact of a history of substance abuse on adherence and access to appropriate antiretroviral therapy. We will also evaluate the effect of a comprehensive adherence-enhancing intervention and document the associations among adherence, treatment failure, and the development of resistance. Specifically, we will: Aim 1. Characterize adherence to HAART among antiretroviral-naive inmates with a history of drug and/or alcohol use incarcerated in the North Carolina Department of Corrections. Aim II. Characterize the effect of a history of drug and/or alcohol use on adherence and the access of inmates to optimal antiretroviral therapy. Aim III. Define the relationship between adherence and viral load in antiretroviral-naive inmates.